Checkpoint immunotherapy that inhibits tumour immune evasion has demonstrated significant clinical success. However, the therapeutic response is limited to certain patient populations, and ...immunotoxicity as well as autoimmunity have compromised the therapeutic benefits. Here, we report on an inherently therapeutic fucoidan-dextran-based magnetic nanomedicine (IO@FuDex
) conjugated with a checkpoint inhibitor (anti-PD-L1) and T-cell activators (anti-CD3 and anti-CD28). IO@FuDex
can repair the immunosuppressive tumour microenvironment by reinvigorating tumour-infiltrating lymphocytes, while targeting the nanomedicine via magnetic navigation to the tumour to minimize off-target effects. Treatment that combines IO@FuDex
and magnetic navigation reduces the occurrence of adverse events and extends the median survival from 32 to 63 days with less than 1 per cent dose compared with soluble anti-PD-L1. Thus, we demonstrate the potential of integrating anti-PD-L1 and T-cell activators as a form of inherently therapeutic nanomedicine to augment the therapeutic index of combination checkpoint immunotherapy.
(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a major global health concern. The increasing prevalence of NAFLD has been related to type 2 diabetes mellitus (T2D). However, the ...relationship between short-chain fatty acids (SCFAs) and NAFLD severity is ambiguous in T2D subjects. This study aimed to explore the association of SCFAs with the severity of NAFLD in T2D patients. (2) Methods: We employed echography to examine the severity of hepatic steatosis. The serum levels of nine SCFAs, namely, formate, acetate, propionate, butyrate, isobutyrate, methylbutyrate, valerate, isovalerate, and methylvalerate, were measured using gas chromatography mass spectrometry. (3) Results: A total of 259 T2D patients was enrolled in this cross-sectional study. Of these participants, 117 with moderate to severe NAFLD had lower levels of formate, isobutyrate, and methylbutyrate than the 142 without NAFLD or with mild NAFLD. Lower circulating levels of isobutyrate and methylbutyrate were associated with an increased severity of NAFLD. A relationship between NAFLD severity and circulating isobutyrate and methylbutyrate levels was found independently of a glycated hemoglobin (HbA1C) level of 7.0%. (4) Conclusion: Circulating levels of isobutyrate and methylbutyrate were significantly and negatively correlated with NAFLD severity in the enrolled T2D patients. SCFAs may be related to NAFLD severity in T2D patients.
Ag-doped Bi2WO6-graphene based photocatalysts were found to exhibit hydrogen production activity. The performance of Bi2WO6-graphene based photocatalysts were investigated and optimized in this ...study. The activity can be further improved by Ag-doping. The morphology, surface chemistry, and phase structure of the photocatalysts were investigated by Field emission scanning electron microscopy, Transmission electron microscopy, X-ray photoelectron spectroscopy, Raman spectra, and X-ray diffraction. UV–vis diffuse reflectance spectroscopy and zeta potential were measured to study the optical properties, bandgap and dispersion stability of the photocatalysts. The effects of forming Bi2WO6-graphene contact and Ag doping on the light absorption, band gap, dispersion stability, and photocatalytic H2 production performance of the composite photocatalysts were evaluated. The improved photocatalytic performance is mainly owing to the Ag doping and high electrical conductivity of graphene.
•Ag doped Bi2WO6–graphene photocatalysts exhibited H2 production activity.•H2 production activity was improved by Ag doping and forming Bi2WO6-graphene contact.•Ag doping leads to decreased bandgap and increased light absorption.•Dispersion stability of Ag-doped sample deteriorated due to decreased zeta potential.•80% activity can be retained when the photocatalyst was recycled after 3 cycles.
Abstract
Effective water use is currently a critical global challenge needed to prevent water shortages and has attracted significant research attention. The realization of solar-driven water ...evaporation by using effective converters has attracted considerable attention in recent years owing to its potential for seawater desalination and wastewater treatment. Consequently, this paper proposes a simple two-step method to prepare low-cost and self-floating photothermal converters from waste coffee grounds. First, the coffee grounds were carbonized at 1,000 °C to develop broadband absorption, and the carbonized coffee grounds were modified using hydrophobic silane to enhance the water-floatation property of the grounds. The prepared hydrophobic carbonized coffee grounds exhibited good performance for desalination and water purification under sunlight irradiation. The self-floatation ability, low cost, well solar evaporation performance, and easy preparation contribute to the promising potential of using hydrophobic carbonized coffee grounds infuture steps toward eco-friendly desalination procedures.
It is known cancer cells secrete cytokines inducing normal fibroblasts (NFs) to become carcinoma-associated fibroblasts (CAFs). However, it is not clear how the CAF-promoting cytokines can ...effectively navigate the dense ECM, a diffusion barrier, in the tumor microenvironment to reach NFs during the early stages of cancer development. In this study, we devised a 3D coculture system to investigate the possible mechanism of CAF induction at early stages of breast cancer. We found that in a force-dependent manner, ECM fibrils are radially aligned relative to the tumor spheroid. The fibril alignment enhances the diffusion of exosomes containing CAF-promoting cytokines towards NFs. Suppression of force generation or ECM remodeling abolishes the enhancement of exosome diffusion and the subsequent CAF induction. In summary, our finding suggests that early-stage, pre-metastatic cancer cells can generate high forces to align the ECM fibrils, thereby enhancing the diffusion of CAF-promoting exosomes to reach the stroma and induce CAFs.
In recent years, techniques of using system disturbance data to validate generator models have been widely discussed. Dynamic model validation and calibration is becoming one of the important ...applications to smart grid initiative. As this kind of technique is utilized to validate generator model, procedures of data screening and reprocessing are essential because raw data obtained from measurement is not always satisfactory. Regarding model parameter calibration, system model is usually quite complicated with various parameters interacting with each other. Artificial intelligent tool is the prior option to save the laborious tuning process and enhance the parameter accuracy. This paper presents a guideline to validate and calibrate parameters of generating units using the record data from phasor measurement unit. Associated procedures for signal filtering on the measurement data, key parameters screening, intelligent search of model parameters, and cross check of legitimate parameters will be discussed in detail. Finally, two historical disturbance cases that happened in the Taiwan power (Taipower) system are applied in accordance with the proposed guideline to demonstrate its effectiveness on generator parameter validation and calibration.
Abstract
Background
Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to ...compare the predictive performance of different candidate biomarkers for AKI.
Methods
In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence.
Results
We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio DOR 16.2, 95% CI 10.1–25.9), urinary NGAL (DOR 13.8, 95% CI 10.2–18.8), and serum NGAL (DOR 12.6, 95% CI 9.3–17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively.
Conclusions
Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients.
Trial registration
CRD42020207883
, October 06, 2020.
Objective
Although the microenvironment for peripheral nerve regeneration is permissive, such a mechanism is defective in diabetes, and the molecular mediators remain elusive. Correction added on May ...11, 2022, after first online publication: In the preceding sentence, “is ok” was changed to “is defective”. This study aimed to (1) investigate the relationship between skin innervation and collagen pathology in diabetic neuropathy and to (2) clarify the molecular alterations that occur in response to hyperglycemia and their effects on axon regeneration.
Methods
We addressed this issue using two complementary systems: (1) human skin from patients with diabetic neuropathy and to (2) a coculture model of human dermal fibroblasts (HDFs) with rat dorsal root ganglia neurons in the context of intrinsic neuronal factor and extrinsic microenvironmental collagen and its biosynthetic pathways.
Results
In diabetic neuropathy, the skin innervation of intraepidermal nerve fiber density (IENFd), a measure of sensory nerve degeneration, was reduced with similar expression of a growth associated protein 43, a marker of nerve regeneration. In contrast, the content and packing of collagen in the diabetic skin became more rigid than the control skin. Sec31a, a protein that regulates the collagen biosynthetic pathway, was upregulated and inversely correlated with IENFd. In the cell model, activated HDFs exposed to high‐glucose medium enhanced the expression of Sec31a and collagen I through the activation of transforming growth factor β, a profibrotic molecule. Sec31a upregulation impaired neurite outgrowth. This effect was reversed by silencing Sec31a expression and neurite outgrowth was resumed.
Interpretation
The current study provides evidence that Sec31a plays a key role in inhibiting nerve regeneration in diabetic neuropathy. ANN NEUROL 2022;91:821–833
To compare on-treatment and off-treatment parameters acquired using acoustic radiation force impulse elastography, the Fibrosis-4 (FIB-4) index, and aspartate aminotransferase-to-platelet ratio index ...(APRI) in patients with chronic hepatitis C (CHC).
Patients received therapies based on pegylated interferon or direct-acting antiviral agents. The changes in paired patient parameters, including liver stiffness (LS) values, the FIB-4 index, and APRI, from baseline to sustained virologic response (SVR) visit (24 weeks after the end of treatment) were compared. Multiple regression models were used to identify significant factors that explained the correlations with LS, FIB-4, and APRI values and SVR.
A total of 256 patients were included, of which 219 (85.5%) achieved SVR. The paired LS values declined significantly from baseline to SVR visit in all groups and subgroups except the nonresponder subgroup (n = 10). Body mass index (P = 0.0062) and baseline LS (P < 0.0001) were identified as independent factors that explained the LS declines. Likewise, the baseline FIB-4 (P < 0.0001) and APRI (P < 0.0001) values independently explained the declines in the FIB-4 index and APRI, respectively. Moreover, interleukin-28B polymorphisms, baseline LS, and rapid virologic response were identified as independent correlates with SVR.
Paired LS measurements in patients treated for CHC exhibited significant declines comparable to those in FIB-4 and APRI values. These declines may have correlated with the resolution of necroinflammation. Baseline LS values predicted SVR.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Electrocardiogram (ECG) biometric provides an authentication to identify an individual on the basis of specific cardiac potential measured from a living body. Convolutional neural networks (CNN) ...outperform traditional ECG biometrics because convolutions can produce discernible features from ECG through machine learning. Phase space reconstruction (PSR), using a time delay technique, is one of the transformations from ECG to a feature map, without the need of exact R-peak alignment. However, the effects of time delay and grid partition on identification performance have not been investigated. In this study, we developed a PSR-based CNN for ECG biometric authentication and examined the aforementioned effects. Based on a population of 115 subjects selected from the PTB Diagnostic ECG Database, a higher identification accuracy was achieved when the time delay was set from 20 to 28 ms, since it produced a well phase-space expansion of P, QRS, and T waves. A higher accuracy was also achieved when a high-density grid partition was used, since it produced a fine-detail phase-space trajectory. The use of a scaled-down network for PSR over a low-density grid with 32 × 32 partitions achieved a comparable accuracy with using a large-scale network for PSR over 256 × 256 partitions, but it had the benefit of reductions in network size and training time by 10 and 5 folds, respectively.
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